Abstract

In parallel with the rising prevalence of metabolic syndrome globally, nonalcoholic fatty liver (NAFL) disease is the most common chronic liver disease in Western countries and nonalcoholic steatohepatitis (NASH) has become increasingly associated with hepatocellular carcinoma. Recent studies have identified NASH as the most rapidly growing indication for liver transplantation (LT). As a hepatic manifestation of the metabolic syndrome, NAFL disease can be histologically divided into NAFL and NASH. NAFL is considered a benign condition, with histological changes of hepatocyte steatosis but without evidence of hepatocellular injury or fibrosis. This is distinct from NASH, which is characterized by hepatocyte ballooning and inflammation, and which can progress to fibrosis and cirrhosis, hepatocellular carcinoma, and liver failure. As for any other end-stage liver disease, LT is a curative option for NASH after the onset of decompensated cirrhosis or hepatocellular carcinoma. Although some studies have suggested increased rates of sepsis and cardiovascular complications in the immediate postoperative period, the long-term posttransplant survival of NASH cases is similar to other indications for LT. Recurrence of NAFL following LT is common and can be challenging, although recurrence rates of NASH are lower. The persistence or progression of metabolic syndrome components after LT are likely responsible for NASH recurrence in transplanted liver. Therefore, while maintaining access to LT is important, concerted effort to address the modifiable risk factors and develop effective screening strategies to identify early stages of disease are paramount to effectively tackle this growing epidemic.

Abstract

BACKGROUND AND AIMS: While the association between platelet activation and hepatic fibrosis has been previously demonstrated in animal studies; the utility of anti-platelet agents in reversing the progression of hepatic fibrosis requires further review. Utilizing systematic review methods, we provide to our knowledge the first meta-analysis combining evidence from all studies aimed to establish the effect of anti-platelet agents in the prevention of hepatic fibrosis.METHODS: We searched Medline, EMBASE and PubMed databases from inception to October 2018 to identify all studies aimed at evaluating the role of anti-platelet agents in the prevention of hepatic fibrosis. The primary outcome was hepatic fibrosis. The initial title, abstract, and full-text screening were performed in duplicate. Risk of bias was evaluated using the Newcastle-Ottawa Scale. A fixed-effect generic inverse variance method was used to create a pooled estimate of the odds of hepatic fibrosis in patients with anti-platelet agents versus without anti-platelet agents.RESULTS: Among the 2310 unique articles identified during the title screening, 4 studies with a combined population of 3141 patients were deemed eligible for inclusion into the meta-analysis establishing the effect of anti-platelet agents on hepatic fibrosis. One study failed to report their findings in the entire cohort, electing to instead summarize the effects of anti-platelets within subgroups categorized by fibrotic risk factors. Use of anti-platelets was associated with 32% decreased odds of hepatic fibrosis, (adjusted pooled OR 0.68; CI 0.56-0.82, p≤0.0001). The statistical heterogeneity among the studies was insignificant.CONCLUSION: Use of anti-platelet agents is associated with the decreased odds of hepatic fibrosis. Due to limited evidence, future high-quality randomized controlled trials with larger comparative samples are required to further delineate the potential beneficial effects of these drugs in preventing hepatic fibrosis.

Abstract

Liver transplantation is lifesaving for patients with severe acute alcoholic hepatitis (SAH) with preliminary data demonstrating favorable early post-transplant outcomes. Using the United Network for Organ Sharing database, we demonstrate that liver transplantation for SAH in the USA has steadily increased and is associated with similar 1- and 3-year post-transplant survival as well as comparable 30-day waitlist mortality to acute liver failure due to drug-induced liver injury.

Abstract

BACKGROUND & AIMS: Little is known about trends in mortality among Hispanic subpopulations and etiologies of chronic liver disease (CLD). We investigated trends in mortality of CLD among the 3 largest Hispanic subgroups based on origin (Mexicans, Puerto Ricans, and Cubans) in the United States (US) from 2007 to 2016.METHODS: We collected data from the US Census and national mortality database, calculated age-standardized mortalities for CLD among Hispanic subgroups, and compared these with non-Hispanic whites. We determined mortality rate patterns by joinpoint analysis with estimates of annual percentage change.RESULTS: Hispanics were relatively younger with a lower likelihood of high school education than non-Hispanic whites at time of death. Puerto Ricans had the highest rates of age-standardized hepatitis C virus-related mortality in 2016, followed by non-Hispanic whites, Mexicans, and Cubans. Age-standardized mortality rates associated with hepatitis B virus infection decreased steadily among all subjects. Age-standardized mortality rates from alcoholic liver disease and nonalcoholic fatty liver disease among non-Hispanic whites and all Hispanics increased and accelerated. Mexicans had the highest rates of age-standardized alcoholic liver disease-related mortality, followed by non-Hispanic whites, Puerto Ricans, and Cubans. Cirrhosis- and hepatocellular carcinoma-related mortality rates increased steadily from 2007 to 2016, with the highest among Puerto Ricans and non-Hispanic whites and Mexicans, and lowest in Cubans.CONCLUSIONS: We found high levels of heterogeneity in CLD-related mortality patterns among the 3 largest Hispanic subgroups. Therefore, combining Hispanics as an aggregate group obscures potentially meaningful heterogeneity in etiology-specific CLD-related mortality rates among Hispanic subgroups.

Abstract

BACKGROUND: Nonalcoholic Steatohepatitis(NASH) is one of the top three indications for liver transplantation in western countries. It is unknown whether renal dysfunction at the time of liver transplantation has any effect on post-liver transplantation outcomes in recipients with NASH.METHODS: From the United Network for Organ Sharing-Standard Transplant Analysis and Research(UNOS-STAR) dataset, we identified 4,088 NASH recipients who received deceased donor liver transplant. We divided our recipients a priori into three categories: Group I with estimated glomerular filtration rate (eGFR)<30 ml/min/1.73m2 at the time of LT and/or received dialysis within 2 weeks preceding LT(n=937); Group II included recipients who had eGFR≥30 ml/min/1.73m2 and did not receive renal replacement therapy prior to LT(n=2,812); and Group III included recipients who underwent SLK transplantation(n=339). We examined the association of pre-transplant renal dysfunction with death with functioning graft, all-cause mortality, and graft loss using competing risk regression and Cox proportional hazards models.RESULTS: The mean±SD age of the cohort at baseline was 58±8 years, 55% were male, 80% were Caucasian, and average exception MELD score was 24±9. The median follow-up period was 5 years (median=1,816 days, interquartile range (IQR):1,090-2,723 days). Compared to Group I recipients, Group II recipients had 19% reduced trend for risk for death with functioning graft[Sub-Hazard Ratio(SHR)(95% CI):0.81(0.64-1.02)] and similar risk for graft loss [SHR(95% CI):1.25(0.59-2.62)] while Group III recipients had similar risk for death with functioning graft[SHR(95% CI):1.23(0.96-1.57)] and graft loss [SHR(95% CI):0.18(0.02-1.37)] using adjusted competing risk regression model.CONCLUSIONS: Recipients with preserved renal function before liver transplantation showed trend toward lower risk of death with functioning graft compared to SLK recipients and those with pre-transplant severe renal dysfunction in patients with NASH. This article is protected by copyright. All rights reserved.

Abstract

BACKGROUND: In the United States, alcoholic liver disease (ALD) has recently become the leading indication for liver transplantation (LT).METHODS: Using the United Network for Organ Sharing registry, we examined temporal trends in adult liver transplant waitlist registrants and recipients with chronic liver disease (CLD) due to ALD from 2007 to 2016.RESULTS: From 2007 to 2016, ALD accounted for 20.4% (18 399) of all CLD waitlist (WL) additions. The age-standardized ALD WL addition rate was 0.459 per 100 000 US population in 2007; nearly doubled to 0.872 per 100 000 US population in 2016 and increased with an average annual percent change of 47.56% (95% CI: 30.33% to 64.72%).The ALD WL addition rate increased over twofold among young (18-39 years) and middle-aged (40-59 years) adults during the study period. Young adult ALD WL additions presented with a higher severity of liver disease including Model for End-Stage Liver Disease score compared to middle aged and older adults (> 60 years). The number of annual ALD WL deaths readily rose from 2014 to 2016, despite an overall annual decline in all CLD WL deaths. Severe hepatic encephalopathy, low BMI (< 18.5) and diabetes mellitus were significant predictors for 1-year waitlist mortality.CONCLUSION: ALD-related WL registrations and LT have increased over the past decade with a disproportionate increase in young and middle-aged adults. These subpopulations within the ALD cohort need to be evaluated in future studies to improve our understanding of factors associated with these alarming trends.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is characterized by histological evidence of hepatic steatosis, lobular inflammation, ballooning degeneration and hepatic fibrosis in the absence of significant alcohol use and other known causes of chronic liver diseases. NAFLD is subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is generally benign but can progress to NASH, which carries a higher risk of adverse outcomes including cirrhosis, end-stage liver disease, hepatocellular carcinoma and death if liver transplantation is not pursued in a timely fashion. Currently, lifestyle modifications including healthy diet and increased physical activity/exercise culminating in weight loss of 5% to >10% is the cornerstone of treatment intervention for patients with NAFLD. Patients with NAFLD who fail to obtain this goal despite the help of dietitians and regimented exercise programs are left in a purgatory state and remain at risk of developing NASH-related advance fibrosis. For such patients with NAFLD who are overweight and obese, healthcare providers should consider a trial of FDA-approved anti-obesity medications as adjunct therapy to provide further preventative and therapeutic options as an effort to reduce the risk of NAFLD-related disease progression.

Abstract

The Asian-American population is characterized by remarkable diversity. Studying Asians as an aggregate group may obscure clinically-meaningful heterogeneity. We performed a population-based study using data from the United States (US) National Vital Statistics System. We determined the trends in age-standardized mortality rates for chronic liver disease stratified by etiology among the most populous US-based Asian subgroups (Asian Indians, Chinese, Filipino, Japanese, Korean, and Vietnamese) and compared it to non-Hispanic whites. Annual percentage change was calculated to determine temporal mortality patterns using joinpoint analysis.Hepatitis C virus-related mortality rates were higher in non-Hispanic whites compared to individual Asian subgroups, but a sharp decline in mortality rates was noted in 2014 among non-Hispanic whites and all Asian subgroups. Age-standardized hepatitis B virus-related mortality rates were higher in all Asian subgroups as compared to non-Hispanic whites in 2016, with the highest mortality among Vietnamese followed by Chinese. Mortality rates for alcoholic liver disease have been steadily trending upwards in all Asian subgroups, with the highest mortality in Japanese. Overall, age-standardized cirrhosis-related mortality rates were highest in non-Hispanic whites, followed by Japanese, and more distantly by Vietnamese and other subgroups. However, hepatocellular carcinoma-related mortality rates were higher in most Asian subgroups led by Vietnamese, Japanese and Koreans compared to non-Hispanic whites. In this population-based study utilizing a nationally representative database, we demonstrated a marked heterogeneity in the mortality rates of etiology-specific chronic liver disease among Asian subgroups in the US. This article is protected by copyright. All rights reserved.

Abstract

With recent improvements in the treatment of end-stage liver disease (ESLD), a better understanding of the burden of cirrhosis and hepatocellular carcinoma (HCC) is needed in the United States (US). A population-based study using the US Census and national mortality database was performed. We identified the age-standardized etiology-specific mortality rates for cirrhosis and HCC among US adults aged ≥ 20 years from 2007 to 2016. We determined temporal mortality rate patterns by joinpoint analysis with estimates of annual percentage change (APC). Age-standardized cirrhosis-related mortality rates increased from 19.77/100,000 persons in 2007 to 23.67 in 2016 with an annual increase of 2.3% (95% CI 2.0-2.7). The APC in mortality rates for hepatitis C virus (HCV)-cirrhosis shifted from a 2.9% increase per year during 2007-2014 to a 6.5% decline per year during 2014-2016. Meanwhile, mortality for cirrhosis from alcoholic liver disease (ALD, APC 4.5%) and nonalcoholic fatty liver disease (NAFLD, APC 15.4%) increased over the same period, while mortality for hepatitis B virus (HBV)-cirrhosis decreased with an average APC of -1.1%. HCC-related mortality increased from 3.48/100,000 persons in 2007 to 4.41 in 2016 at an annual rate of 2.0% (95% CI 1.3-2.6). Etiology-specific mortality rates of HCC were largely consistent with cirrhosis-related mortality. Minority populations had a higher burden of HCC-related mortality.CONCLUSION: Cirrhosis- and HCC-related mortality rates increased between 2007 and 2016 in the US. However, mortality rates in HCV-cirrhosis demonstrated a significant decline from 2014-2016, during the direct-acting antiviral era. Mortality rates for ALD/NAFLD-cirrhosis and HCC have continued to increase, while HBV-cirrhosis-related mortality declined during the 10-year period. Importantly, minorities had a disproportionately higher burden of ESLD-related mortality. This article is protected by copyright. All rights reserved.

Abstract

BACKGROUND & AIMS: Although treatment of hepatitis C virus (HCV) infection has improved, the prevalence of alcoholic liver disease (ALD) has been increasing, so we need an updated estimate of the burden and etiology-specific mortality of chronic liver diseases. We studied the trends in age-standardized mortality of chronic liver diseases among adults 20 years or older in the United States (US), from 2007 through 2016.METHODS: We collected data from the US Census and National Center for Health Statistics mortality records, identifying individuals with HCV infection, ALD, nonalcoholic fatty liver disease (NAFLD), or hepatitis B virus (HBV) infection using ICD-10 codes. We obtained temporal mortality rate patterns using joinpoint trend analysis with estimates of annual percentage change (APC).RESULTS: Age-standardized HCV-related mortality increased from 7.17/100,000 persons in 2007 to 8.14/100,000 persons in 2013, followed by a marked decrease in the time period at which patients began receiving treatment with direct-acting antiviral agents (from 8.09/100,000 persons in 2014 to 7.15/100,000 persons in 2016). The APC in HCV mortality increased 2.0%/year from 2007 through 2014, but decreased 6.4%/year from 2014 through 2016. In contrast, age-standardized mortality increased for ALD (APC of 2.3% from 2007 through 2013 and APC of 5.5% from 2013 through 2016) and NAFLD (APC of 6.1% from 2007 through 2013 and APC of 11.3% from 2013 through 2016). HBV-related mortality decreased steadily from 2007 through 2016, with an average APC of -2.1% (95% CI, -3.0 to -1.2). Etiology-based mortality in minority populations were higher. HCV-related mortality (per 100,000 persons) was highest among non-Hispanic blacks (10.28) and whites (6.92), followed by Hispanics (5.94), and lowest among non-Hispanic Asians (2.33). Non-Hispanic Asians had higher mortality for HBV infection (2.82 per 100,000 vs 1.02 for non-Hispanic blacks, and 0.47 for non-Hispanic whites).CONCLUSION: In our population-based analysis of chronic liver disease mortality in the US, the decline in HCV-related mortality coincided with the introduction of direct-acting antiviral therapies, while the mortality from ALD and NAFLD increased during the same period. Minorities in the US have disproportionately higher chronic liver disease-related mortality.

Abstract

In recent years, the opioid epidemic and new hepatitis C virus (HCV) treatments have changed the landscape of organ procurement and allocation. We studied national trends in solid organ transplantation (2000⁻2016), focusing on graft utilization from HCV seropositive deceased donors in the pre-2014 (2000⁻2013) versus current (2014⁻2016) eras with a retrospective analysis of the United Network for Organ Sharing database. During the study period, HCV seropositive donors increased from 181 to 661 donors/year. The rate of HCV seropositive donor transplants doubled from 2014 to 2016. Heart and lung transplantation data were too few to analyze. A higher number of HCV seropositive livers were transplanted into HCV seropositive recipients during the current era: 374 versus 124 liver transplants/year. Utilization rates for liver transplantation reached parity between HCV seropositive and non-HCV donors. While the number of HCV seropositive kidneys transplanted to HCV seropositive recipients increased from 165.4 to 334.7 kidneys/year from the pre-2014 era to the current era, utilization rates for kidneys remained lower in HCV seropositive than in non-HCV donors. In conclusion, relative underutilization of kidneys from HCV seropositive versus non-HCV donors has persisted, in contrast to trends in liver transplantation.

Abstract

The prevalence of latent tuberculosis infection (LTBI) in the United States in 2011 and 2012 was estimated at 4.4⁻4.8%. As of 2015, 12.4 million people still possessed LTBI. Isoniazid, or isonicotinic acid hydrazine (INH), is the most commonly used medication among varying regimens that exist in the treatment of tuberculosis and LTBI. INH-related hepatotoxicity is a well-known adverse effect of its use, often causing asymptomatic elevations in serum aminotransferase levels. These elevations are typically transient and reversible, but can cause acute, clinically-significant liver injury in rare cases. We report a case of a 67-year old male who developed subacute hepatic injury secondary to INH treatment for LTBI, and ultimately underwent liver transplantation due to the progression to hepatic decompensation, despite withdrawal of the medication. Because symptoms of INH hepatotoxicity are nonspecific and prognosis can be variable, clinicians must maintain a high index of suspicion for this adverse effect. As exemplified by this case, early recognition may be life-saving.

Abstract

Non-alcoholic fatty liver disease (NAFLD), the most common cause of liver disease, affects approximately 75 to 100 million Americans. Patients with concurrent NAFLD and type 2 diabetes mellitus have a higher risk of progressing to advanced fibrosis and non-alcoholic steatohepatitis compared to non-diabetics. Lifestyle modifications, including weight loss, remain the mainstay of treatment for NAFLD, as there are no medications currently indicated for this disease state. Anti-diabetic pharmacologic therapies aimed at improving insulin sensitivity and decreasing insulin production have been studied to determine their potential role in slowing the progression of NAFLD. In this review, we focus on the evidence surrounding anti-diabetic medications and their ability to improve disease progression in patients with NAFLD.

Abstract

BACKGROUND & AIMS: Data on the differences in ethnicity and race among patients with primary biliary cholangitis (PBC) awaiting liver transplantation (LT) are limited. We evaluated liver transplant waitlist trends and outcomes based on ethnicity and race in patients with PBC in the United States.METHODS: Using the United Network for Organ Sharing (UNOS) registry, we collected data on patients with PBC on the liver transplant waitlist, and performed analysis with a focus on ethnicity and race-based variations clinical manifestations, waitlist mortality and LT rates from 2000 to 2014. Outcomes were adjusted for demographics, complications of portal hypertension, and Model for End-stage Liver Disease score at time of waitlist registration.RESULTS: Although the number of white PBC waitlist registrants and additions decreased from 2000 to 2014, there were no significant changes in the number of Hispanic PBC waitlist registrants and additions each year. The proportion of Hispanic patients with PBC on the liver transplant waitlist increased from 10.7% in 2000 to 19.3% in 2014. Hispanics had the highest percentage of waitlist deaths (20.8%) of any ethnicity or race evaluated. After adjusting for demographic and clinical characteristics, Hispanic patients with PBC had the lowest overall rate for undergoing LT (adjusted hazard ratio, 0.71; 95% CI, 0. 60-0.83; P < .001) and a significantly higher risk of death while on the waitlist, compared to whites (adjusted hazard ratio, 1.41; 95% CI, 1.15-1.74; P < .001). Furthermore, Hispanic patients with PBC had the highest proportion of waitlist removals due to clinical deterioration.CONCLUSIONS: In an analysis of data from UNOS registry focusing on outcomes, we observed differences in rates of LT and liver transplant waitlist mortality of Hispanic patients compared with white patients with PBC. Further studies are needed to improve our understanding of ethnicity and race-based differences in progression of PBC.

Abstract

Since the advent of direct acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant (LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response (SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.

Abstract

GOALS: The goal of this study was to evaluate the impact of inpatient outcomes of gastrointestinal bleeding (GIB) related to percutaneous coronary intervention (PCI).BACKGROUND: With all-cause mortality increasing in patients undergoing PCIs, outcomes for GIB associated with PCI may be adversely impacted.STUDY: Using the National Inpatient Sample (2007 to 2012), we performed a nested case-control study assessing inpatient outcomes including incidence and mortality for PCI-related GIB hospitalizations. Multivariate logistic regression analyses were performed to determine significant predictors for GIB incidence and mortality.RESULTS: A total of 9332 (1.2%) of PCI hospitalizations were complicated by GIB with the age-adjusted incidence rate increasing 13% from 2007 (11.3 GIB per 1000 PCI) to 2012 (12.8). Patients ≥75 years of age experienced the steepest incline in GIB incidence, which increased 31% during the study period. Compared with non-GIB patients, mean length of stay (9.4d vs. 3.3d) and median cost of care ($29,236 vs. $17,913) was significantly higher. Significant demographic risk factors for GIB included older age and comorbid risk factors included gastritis or duodenitis, and Helicobacter pylori infection.In total, 1044 (11%) of GIB patients died during hospitalization with the GIB mortality rate increasing 30% from 2007 (95 deaths per 1000 GIB) to 2012 (123). Older age had the strongest association with inpatient mortality.CONCLUSIONS: Inpatient incidence and mortality for PCI-related GIB has been increasing particularly with a large increase in incidence among older patients. A multidisciplinary approach focused on risk-stratifying patients may improve preventable causes of GIB.

Abstract

Nonalcoholic steatohepatitis (NASH) is a rapidly growing etiology of end-stage liver disease in the US. Temporal trends and outcomes in NASH-related liver transplantation (LT) in the US were studied.A retrospective cohort study utilizing the United Network for Organ Sharing and Organ Procurement and Transplantation (UNOS/OPTN) 2003-2014 database was conducted to evaluate the frequency of NASH-related LT. Etiology-specific post-transplant survival was evaluated with Kaplan-Meier methods and multivariate Cox proportional hazards models.Overall, 63,061 adult patients underwent LT from 2003 to 2014, including 20,782 HCV (32.96%), 9470 ALD (15.02%), and 8262 NASH (13.11%). NASH surpassed ALD and became the second leading indication for LT beginning in 2008, accounting for 17.38% of LT in 2014. From 2003 to 2014, the number of LT secondary to NASH increased by 162%, whereas LT secondary to HCV increased by 33% and ALD increased by 55%. Due to resurgence in ALD, the growth in NASH and ALD was comparable from 2008 to 2014 (NASH +50.15% vs. ALD +41.87%). The post-transplant survival in NASH was significantly higher compared to HCV (5-year survival: NASH -77.81%, 95% CI 76.37-79.25 vs. HCV -72.15%, 95% CI 71.37-72.93, P

Abstract

Prophylactic antibiotics have been recommended in patients with a previous history of spontaneous bacterial peritonitis (SBP). Recently, there has been interest in the use of rifaximin for the prevention of SBP and hepatorenal syndrome (HRS). We conducted a meta-analysis to evaluate this association of rifaximin. We searched several databases from inception through 24 January 2017, to identify comparative studies evaluating the effect of rifaximin on the occurrence of SBP and HRS. We performed predetermined subgroup analyses based on the type of control group, design of the study, and type of prophylaxis. Pooled odds ratios (ORs) were calculated using a random effects model. We included 13 studies with 1703 patients in the meta-analysis of SBP prevention. Pooled OR [95% confidence interval (CI)] was 0.40 (95% CI: 0.22-0.73) (I=58%). On sensitivity analysis, adjusted OR was 0.29 (95% CI: 0.20-0.44) (I=0%). The results of the subgroup analysis based on type of control was as follows: in the quinolone group, pooled OR was 0.42 (95% CI: 0.14-1.25) (I=55%), and in the no antibiotic group, pooled OR was 0.40 (95% CI: 0.18-0.86) (I=64%). However, with sensitivity analysis, benefit of rifaximin was demonstrable; pooled ORs were 0.32 (95% CI: 0.17-0.63) (I=0%) and 0.28 (95% CI: 0.17-0.45) (I=0%) for the comparison with quinolones and no antibiotics, respectively. Pooled OR based on randomized controlled trials was 0.41 (95% CI: 0.22-0.75) (I=13%). For the prevention of HRS, the pooled OR was 0.25 (95% CI: 0.13-0.50) (I=0%). Rifaximin has a protective effect against the development of SBP in cirrhosis. However, the quality of the evidence as per the GRADE framework was very low. Rifaximin appeared effective for the prevention of HRS.

Abstract

We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945-1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a retrospective analysis using the United Network for Organ Sharing (UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare HCC-related liver transplant surgery trends between two cohorts-the BB and non-BB-with a secondary diagnosis of HCV, ALD, or NASH. From 2003-2014, there were a total of 8313 liver transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658 (80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%) during the study period. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and NASH suggests the need for increased awareness and improved preventative screening/surveillance measures within NASH and ALD cohorts as well.

Abstract

Statins may improve outcomes in patients with chronic liver disease (CLD). We conducted a systematic review and meta-analysis to evaluate the impact of statins in the setting of CLD.We searched several databases from inception to 17 October 2016 to identify comparative studies evaluating the role of statins in CLD. Outcomes of interest were the associations between statin use and progression of fibrosis, development of hepatic decompensation in cirrhosis, and mortality in CLD. Adjusted hazard ratios (HRs) were pooled and analyzed using a random effects model. Subgroup analyses were performed based on the method of detection for progression of hepatic fibrosis and quality of studies.We included 10 studies (1 randomized controlled trial and 9 observational) with 259,453 patients (54,441 statin users and 205,012 nonusers). For progression of hepatic fibrosis, pooled HR (95% confidence interval) was 0.49 (0.39-0.62). On subgroup analysis of studies using ICD-9 (The International Classification of Diseases, Ninth Revision) coding and a second method to detect cirrhosis, pooled HR was 0.58 (0.51-0.65); pooled HR for studies using ICD-9 coding only was 0.36 (0.29-0.44). For progression of fibrosis in patients with hepatitis C virus (HCV) infection, pooled HR was 0.52 (0.37-0.73). For hepatic decompensation in cirrhosis, pooled HR was 0.54 (0.46-0.65). For mortality, pooled HR based on observational studies was 0.67 (0.46-0.98); in the randomized controlled trial, HR was 0.39 (0.15-0.99). However, the quality of evidence for these associations is low as most included studies were retrospective in nature and limited by residual confounding.Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with CLD. As the quality (certainty) of evidence is low, further studies are needed before statins can be routinely recommended.Am J Gastroenterol advance online publication, 6 June 2017; doi:10.1038/ajg.2017.170.

Abstract

Recently, we reported the successful application of task-shifting to improve the management of patients with chronic hepatitis C virus (HCV) infection receiving treatment with direct-acting antiviral (DAA) agents in underserved areas of California. We assessed the impact of e-health on task-shifting in our treatment model.In a retrospective analysis, we reviewed the impact of e-health on optimizing the delivery of DAA-based regimen to HCV-infected patients in outreach clinics in medically underserved areas of California. A nonphysician healthcare provider worked in close conjunction with a hepatologist to monitor the patients during the course of antiviral therapy. We exclusively used our institution-based, secured e-health portal as the means of communication with the local staff and patients in outreach clinics.From January 2015 to June 2016, we treated over 100 HCV-infected patients with DAA-based regimens using the task-shifting model. During the study period, we did not experience any delay in the care of our patients undergoing treatment with DAA agents. Communication with the patient and staff using e-health was prompt, secured, and documented in electronic medical records. Due to the optimization of task-shifting by e-health and safety/tolerability of DAA, 95% patients did not need a follow-up clinic visit during the treatment. Return clinic visits during the treatment were unrelated to DAA use or associated with ribavirin-related anemia. In addition, we noted improvement in access and capacity of our outreach clinic.We report a positive impact of e-health in optimizing task-shifting for DAA in HCV-infected patients in underserved outreach clinics. More importantly, a secondary improvement in access and capacity of our clinic was noted.

Abstract

All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with Hepatitis C (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre- vs. post-LT. The objective of this study was to analyze the cost-effectiveness of pre- vs. post-LT treatment with an all-oral DAA regimen among HCV patients with HCC (hepatocellular carcinoma) or DCC (decompensated cirrhosis).We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted (WL) for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age 50 over a 30 year time horizon from a third-party US payer perspective, and estimated their health and cost outcomes based on pre- vs. post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained viral response (SVR) rates were sourced from ASTRAL-4 and SOLAR-1, -2. Costs were sourced from RedBook, Medicare fee schedules, and published literature.In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years (QALYs) and $365,948 per patient lifetime costs vs. 10.39 and $283,696 in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy results in 9.27 per-patient QALYs and $304,800 per patient lifetime costs vs. 8.7 and $283,789 in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed results were most sensitive to the utility of patients post-LT, treatment SVR rates, LT costs, and baseline MELD score (DCC analysis only).The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research. Our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. This article is protected by copyright. All rights reserved.

Abstract

Hepatic encephalopathy (HE) is a complex disease requiring a multidisciplinary approach among specialists, primary care team, family, and caregivers. HE is currently a diagnosis of exclusion, requiring an extensive workup to exclude other possible etiologies, including mental status changes, metabolic, infectious, traumatic, and iatrogenic causes. The categorization of HE encompasses a continuum, varying from the clinically silent minimal HE (MHE), which is only detectable using psychometric tests, to overt HE, which is further divided into four grades of severity. While there has been an increased effort to create fast and reliable methods for the detection of MHE, screening is still underperformed due to the lack of standardization and efficient methods of diagnosis. The management of HE requires consultation from various disciplines, including hepatology, primary care physicians, neurology, psychiatry, dietician/nutritionist, social workers, and other medical and surgical subspecialties based on clinical presentation and clear communication among these disciplines to best manage patients with HE throughout their course. The first-line therapy for HE is lactulose with or without rifaximin. Following the initial episode of overt HE, secondary prophylaxis with lactulose and/or rifaximin is indicated with the goal to prevent recurrent episodes and improve quality of life. Recent studies have demonstrated the negative impact of MHE on quality of life and clinical outcomes. In light of all this, we emphasize the importance of screening and treating MHE in patients with liver cirrhosis, particularly through a multidisciplinary team approach.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The rising incidence, genetic heterogeneity, multiple etiologies, and concurrent chronic liver diseases make diagnosis, staging, and selection of treatment options challenging in patients with HCC. The best approach to optimize the management of HCC is one that utilizes a core multidisciplinary liver tumor board, consisting of hepatologists, pathologists, interventional radiologists, oncologists, hepatobiliary and transplant surgeons, nurses, and general practitioners. In most cases, HCC is diagnosed by abdominal imaging studies, preferably with a triphasic computed tomography scan of the abdomen or magnetic resonance imaging of the abdomen. Histopathological diagnosis using a guided liver biopsy may be needed in noncirrhotic patients or when radiological diagnostic criteria are not fulfilled in the setting of cirrhosis. The Barcelona Clinic Liver Cancer staging system facilitates a standardized therapeutic strategy based on the tumor burden, extent of metastasis, severity of hepatic decompensation, comorbid medical illnesses, functional status of patient, HCC-related symptoms, and preference of the patient. Treatment options include curative surgery (hepatic resection and liver transplantation) and palliative measures (radiofrequency ablation, transarterial chemoembolization, and chemotherapy with sorafenib). The role of the multidisciplinary team is crucial in promptly reconfirming the diagnosis, staging the HCC, and formulating an individualized treatment plan. In potential liver transplant candidates, timely liver transplant evaluation and coordinating bridging/downsizing treatment modalities, such as radiofrequency ablation and transarterial chemoembolization, can be time-consuming. In summary, a multidisciplinary team approach provides a timely, individualized treatment plan, which can vary from curative surgery in patients with early-stage HCC to palliative/hospice care in patients with metastatic HCC. In most tertiary care centers in the US, a multidisciplinary liver tumor board has become the standard of care and a key component of best practice protocol for patients with HCC.

Abstract

Background and Aims: Utilization of living donor liver transplantation (LDLT) and its relationship with recipient Model for End-Stage Liver Disease (MELD) needs further evaluation in the United States (U.S.). We evaluated the association between recipient MELD score at the time of surgery and survival following LDLT. Methods: All U.S. adult LDLT recipients with MELD < 25 were evaluated using the 1995-2012 United Network for Organ Sharing registry. Survival following LDLT was stratified into three MELD categories (MELD < 15 vs. MELD 15-19 vs. MELD 20-24) and evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models. Results: Overall, 2,258 patients underwent LDLT. Compared to patients with MELD < 15, overall 5-year survival following LDLT was similar among patients with MELD 15-19 (80.9% vs. 80.3%, p = 0.77) and MELD 20-24 (81.2% vs. 80.3%, p = 0.73). When compared to patients with MELD < 15, there was no significant difference in long-term post-LDLT survival among those with MELD 15-19 (HR: 1.11, 95% CI: 0.85-1.45, p = 0.45) and a non-significant trend towards lower survival in patients with MELD 20-24 (HR: 1.28, 95% CI: 0.91-1.81, p = 0.16). Only 14% of LDLTs were performed in patients with MELD 20-24 and the remaining 86% in patients with MELD < 20. Conclusion: LDLT is underutilized in patients with MELD 20 and higher.